Description (Applicant Abstract): This research project focuses on the synthesis and characterization of novel base-modified carbon nucleoside analogs and spiroaminoketals. The proposed synthetic design for both compound classes is an extension of a regio- and stereoselective methodology for benzenesulfonyl-tetrahydrofuranylidenes, and alkylidene pyrrolidine synthons that were developed in this laboratory during the past grant period. This project will afford a systematic array of three modified carbon nucleosides derived from D-(+)-ribonic-gamma-lactone differently attached to carbo-, and heterocyclic aglycones of varying degree of polarity, aromaticity and steric demands. The obtained base-modified C-nucleoside analogs will be characterized by spectroscopic methods including nuclear magnetic resonance, infrared, mass spectroscopy, and x-ray diffraction techniques. The effect of the aglycones at C1' will be examined by measurement of the proton-proton coupling constants (3JHH) at different temperatures. It offers an investigation of the basic parameters that determine preferential conformations of nucleosides necessary to understand how the local structure variation takes place in DNA and RNA when the base-modified carbon nucleoside analogs are incorporated into oligonucleotides. This project will also afford spiroaminoketal derivatives as structural units found in molluscicidal, antitumor, antifungal and antiviral natural products. The proposed synthetic methods will give advantages over currently published procedures because of its versatility to provide access to currently important bioactive compounds.